1. Field
The present invention process relates to the production of pharmaceutical grade Melphalans or p-bis-(2-chloroethyl)-aminophenylalanine, by using industrial grade reactants. Melphalans or p-bis-(2- chloroethyl)-aminophenylalanine is a known antineoplastic that inhibits or prevents the development of neoplasms by checking the maturation and proliferation of malignant cells; and this is true for the D and L forms as well as the racemic or the DL form.
2. The Prior Art
In U.S. Pat. No. 3,032,584 there is disclosed a process for the manufacture of p-bis-(2-chloroethyl)-aminophenyalanine which comprises heating a compound of the general formula:
                in which R1 is selected from the group consisting of hydrogen and the COOC2H2 radical, R2 is hydrogen and R3 is selected from the group consisting of CHO and CH3 CO radicals or R2 and R3 together represent the        

radical, with a chlorinating agent selected from the group consisting of phosphorus oxychloride and thionyl chloride.
Another process for production of p-bis-(2-cloroethyl)-aminophenylalanine is disclosed in U.S. Pat. 3,032,585 and comprises:
treating a solution of N-acetyl-p-nitro-DL-phenylalanine with burcine, separating the optical isomers by crystallization of the brucine salt of the L-isomer, basifying a solution of the brucine salt of the L-isomer to precipitate brucine, removing the brucine, acidifying the solution to produce N-acetyl-p-nitro-L-phenylalanine, subjecting this compound to hydrolysis to produce L-p-nitrophenylalanine, esterifying the carboxyl group of the compound, reacting the ester with phthalic anhydride to form the N-phthaloyl derivative, subjecting this to catalytic hydrogenation to reduce the nitro group to an amino group, treating the amino compound with ethylene oxide to effect hydroxyethylation, and then subjecting the product to chlorination with a chlorinating agent selected from the group consisting of phosphorous oxychloride and thionyl chloride followed by hydrolysis for the removal of the phthaloyl group to produce L-p-bis-(2-chloro-ethyl)-aminophenylalanine.
The processes of these two patents do not utilize inexpensive industrial grade reactants to provide pharmaceutical grade Melphalans.
The use of industrial grade reactants to produce pharmaceutical grade Melphalans would make the products far less expensive and therefore available to patients and governments who would otherwise not be able to afford the same.